With more than 12 million new cases of cancer each year, development of new and more effective anticancer therapies is a major priority of pharmaceutical researchers. Targeted delivery of therapeutic agents is particularly important in chemotherapy because anticancer drugs tend to have severe side effects, and anticancer drugs often kill healthy cells.
Both passive and active targeting have been employed in the delivery of anticancer drugs. Passive targeting relies on the enhanced permeability and retention (EPR) effect of cancerous tissues, a result of leaky blood vessels and poor lymphatic drainage. Active targeting depends on functionalizing the surface of the drug carrier with molecules that bind to overexpressed receptors on cancerous cells. Despite the benefits of active and passive targeting, compositions and methods with increased effectiveness are needed to further improve current cancer therapy.
Multivalent interactions frequently occur between biological entities. When strong binding is not possible with a single receptor—ligand pair, multivalency, or simultaneous binding between multiple receptors and ligands, can be an effective strategy to enhance the binding. Multivalent interactions are involved in many diseases, such as the common flu, cancer, and AIDS. Researchers have sought to develop multivalent ligands that can inhibit the binding of host cells by viruses and bacteria. Two of the most widely used scaffolds in multivalency are dendrimers and gold nanoparticles protected with multiple functionalized thiols. However, few clinical applications have been developed from these approaches.
Accordingly, there is a need for improved therapies for conditions that involve multivalent interactions. Multivalent ligands that can inhibit the binding of host cells by viruses, bacteria, and the like, are needed for such therapy. There is also a need for improved methods to prepare multivalent ligands, such as multivalent ligands in the form of nanoparticles.